ESTRO 35 Abstract book

S962 ESTRO 35 2016 _____________________________________________________________________________________________________

Purpose or Objective: Radiation-induced bystander effect (RIBE) has been described only for certain cancer types as the appearance of radiation effects in not directly irradiated cells. This study evaluated the ability of prostate adenocarcinoma (ADC) to induce RIBE exploring the factors that may affect its intensity. The idea was to produce a strong, clinically applicable RIBE, that could lead to development of innovative approaches in modern radiotherapy treatment of prostate cancer, especially for those patients with hormone-refractory ADC in which radiotherapy might have a limited role. Material and Methods: 2 prostate ADC cell lines of different differentiation, PC-3 - hormone-resistant and DU-145 - hormone-sensitive, have been irradiated using wide range of doses (15 cGy-3000 cGy in 1 fraction) to obtain radiation- conditioned medium (RCM) which was then used to “treat” the unirradiated cells and to evaluate the cytokines level. Each sample of RCM was subjected to triple immunoassay assessment of the following cytokines: Eotaxin, Interferon- gamma, Interleukin(IL)-2, IL-4, IL-6, IL-8, IL-10, IL-12, Macrophage Inflammatory Protein-1-alpha, Tumor Necrosis Factor-alpha and Vascular Endothelial Growth Factor. Using a spectrophotometer cell growth was assessed. All comparisons were made to the negative control using paired t-tests. Significance was set at p-value < 0.05, 2-tailed test. Results: Prostate ADC was able to induce RIBE which intensity depended on dose and tumor differentiation grade: the strongest RIBE for PC-3 was achieved with 2000 cGy and for DU-145 with only 15 cGy (Fig.1).

Results: AS released by cells exposed only to H were active affecting proliferation and radio-sensibility of N cells and HR clones. Those effects depended on cell histotype, respiratory status of cell-inducers and cell-recipients of AS (N vs. H) and duration of cell-exposure to H (24 vs. 72h). Depending on time-exposure to H, HIAE promoted both increased and reduced proliferation. The type and intensity of RIAE depended on dose and notably changed if AS were transmitted by N or H irradiated cells (Tab.1, Fig.1).

In H460 RIAE caused radio-resistance, a phenomenon similar to adaptive response but in this case acquired via AS by cells that have never been irradiated. Manipulating the respiratory ambient of cell-receivers of AS the effects of both RIAE and HIAE on proliferation and radio-sensibility changed significantly. The comparative analysis of GF levels with cell proliferation and survival showed a correlation between anti- proliferative sFLT-1 and almost all CM types for both cell lines. Conclusion: Our results proved that exposing of cells to H and irradiation of H cells lead to significant HIAE and RIAE, respectively, which are able to affect cell proliferation and radio-sensibility. Both phenomena depend on several factors whose manipulation is possible and leads to induction of clinically applicable RIAE. EP-2038 Manipulation of radiation-induced bystander effect in prostate adenocarcinoma S. Tubin 1 Landeskrankenhaus Klagenfurt, Radiotherapy, Klagenfurt, Austria 1 , M. Valeriani 2 , M.F. Osti 3 , G. Minniti 3 , S. Bracci 3 , S. Gerardo 4 2 Sant´Andrea Hospital- Rome- La Sapienza University, Radiotherapy, Rome, Italy 3 Sant´Andrea Hospita- Rome- La Sapienza University, Radiotherapy, Rome, Italy 4 Sant´Andrea Hospita- Rome- La Sapienza University, Laboratory Medicine, Rome, Italy

Figure 1. Bystander effect in prostate adenocarcinoma: the strongest proliferative blocking in PC-3 achieved with 20 Gy (left graph) and in DU-145 with 0.15 Gy (right graph) For DU-145 there wasn’t correlation between cytokines level and RIBE intensity while for PC-3 IL-6 correlates with strongest RIBE. The dose required to kill all cells exposed to irradiation was different for 2 cell lines: for DU-145 a lethal dose was reached with 2500 cGy, while PC-3 resisted to 3500 cGy after which tumor repopulation was observed starting 2 weeks after irradiation from just a few survived cells that have undergone particular “giant” differentiation. Conclusion: RIBE intensity can be manipulated by modifying radiation dose and depends on differentiation grade. IL-6 correlates with strongest RIBE after exposure of PC-3 to a very high dose of radiation thus indicates its possible involvement in bystander signals transmission. EP-2039 The impact of surgical wound fluids after IORT on the breast cancer stem cell phenotype W.M. Suchorska 1 Greater Poland Cancer Centre, Radiobiology Lab- Department of Medical Phisics, Poznan, Poland 1,2 , K. Kulcenty 1 , D. Murawa 3 2 Poznan University of Medical Sciences, Department of Electroradiology, Poznan, Poland 3 Greater Poland Cancer Centre, Department Surgical Oncology I, Poznan, Poland Purpose or Objective: Breast cancer is the most common cancer in women. The conventional conservative treatment